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Angiotensin II

Class: Renin-Angiotensin-Aldosterone System (RAAS)
Chemical Name: L-aspartyl-L-arginyl-L-valyl-L-tyrosyl-L-isoleucyl-L-histidyl-L-prolyl-L-phenylalanine acetate salt
Molecular Formula: C50H71N13O12•(C2H4O2)
CAS Number: 68521-88-0
Brands: Giapreza

Medically reviewed by Drugs.com. Last updated on Nov 4, 2019.

Introduction

Vasoconstrictor; synthetic form of endogenous angiotensin II, a peptide hormone of the renin-angiotensin-aldosterone system (RAAS).1 3 4 5 7 9

Uses for Angiotensin II

Shock

Used to increase BP in patients with septic or other distributive shock.1 3 4 5 7

Substantially and rapidly increases mean arterial pressure (MAP) in patients who remain hypotensive despite fluid and vasopressor therapy.1 4

May have a catecholamine-sparing effect, but effects on mortality not established.1 4 6

Angiotensin II Dosage and Administration

General

  • Individualize dosage based on BP response.1

  • Monitor BP and titrate dosage as frequently as every 5 minutes to achieve or maintain target BP.1

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by continuous IV infusion; manufacturer recommends administration via central venous line.1

Dilution

Must dilute commercially available injection concentrate prior to infusion.1

Dilute with 0.9% sodium chloride injection to final concentration of 5000 or 10,000 ng/mL depending on patient's fluid status.1 For patients who are not fluid restricted, prepare concentration of 5000 ng/mL by adding 1 mL (2.5 mg) of the injection concentrate to an infusion bag containing 500 mL of 0.9% sodium chloride injection.1 For fluid-restricted patients, prepare concentration of 10,000 ng/mL by adding 1 mL (2.5 mg) of the injection concentrate to an infusion bag containing 250 mL of 0.9% sodium chloride injection.1

Rate of Administration

Individualize rate of IV infusion based on BP response without exceeding maximum recommended rates.1 (See Prescribing Limits under Dosage and Administration.)

Dosage

Available as angiotensin II acetate; dosage expressed in terms of angiotensin II.1

Adults

Septic or Other Distributive Shock
IV

Initially, 20 ng/kg per minute by continuous IV infusion.1 Titrate based on BP response.1 May increase infusion rate by increments of up to 15 ng/kg per minute as frequently as every 5 minutes as needed to achieve or maintain target BP.1 Do not exceed maximum dosage of 80 ng/kg per minute during the first 3 hours of treatment.1

When underlying shock has improved, titrate dosage downward by decrements of up to 15 ng/kg per minute every 5 to 15 minutes as tolerated to maintain target BP.1 Do not exceed maximum dosage of 40 ng/kg per minute during maintenance therapy.1

Prescribing Limits

Adults

Septic or Other Distributive Shock
IV

First 3 hours of infusion: Maximum 80 ng/kg per minute.1

Maintenance period: Maximum 40 ng/kg per minute.1

Special Populations

Hepatic Impairment

No specific dosage recommendations.1

Renal Impairment

No specific dosage recommendations.1

Geriatric Patients

No specific dosage recommendations.1

Cautions for Angiotensin II

Contraindications

  • Manufacturer states none known.1

Warnings/Precautions

Thrombosis Risk

Increased incidence of arterial and venous thromboembolic events, particularly DVT, reported.1 6

Concurrent use of venous thromboembolism (VTE) prophylaxis recommended.1

Specific Populations

Pregnancy

Insufficient data in pregnant women to determine any drug-associated risks.1 Animal reproductive studies not conducted.1

Septic or other distributive shock is a medical emergency and can be fatal if untreated; a delay in treatment in pregnant women is likely to increase risk of maternal and fetal morbidity and mortality.1

Lactation

Not known whether distributed into milk, affects milk production, or affects the breast-fed infant.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

No substantial differences in safety or efficacy relative to younger adults.1

Hepatic Impairment

Pharmacokinetics not expected to be altered by hepatic impairment.1

Renal Impairment

Pharmacokinetics not expected to be altered by renal impairment.1

Common Adverse Effects

Thromboembolic events (e.g., DVT), thrombocytopenia, tachycardia, fungal infection, delirium, acidosis, hyperglycemia, peripheral ischemia.1

Interactions for Angiotensin II

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

May increase response to angiotensin II1

Angiotensin II receptor antagonists

May decrease response to angiotensin II1

Angiotensin II Pharmacokinetics

Absorption

Bioavailability

Steady-state concentrations achieved in 5 minutes.10

Onset

Following IV infusion, median time to reach target MAP approximately 5 minutes.1

Plasma Concentrations

Following IV infusion in adults with septic or other distributive shock, serum concentrations of angiotensin II were similar at baseline and at 3 hours.1 However, after 3 hours of treatment, serum concentrations of angiotensin I (precursor to angiotensin II) were reduced by approximately 40%.1

Distribution

Extent

Not known whether angiotensin II is distributed into human milk.1

Elimination

Metabolism

Metabolized by aminopeptidase A to angiotensin 2-8 (angiotensin III) and by angiotensin-converting enzyme 2 to angiotensin 1-7 in plasma, erythrocytes, and many other major organs (e.g., intestine, kidney, liver, lungs).1 Angiotensin 1-7 exhibits opposing actions to angiotensin II and causes vasodilation, natriuresis, and reduced BP.1 5 9

Half-life

<1 minute.1

Special Populations

No substantial pharmacokinetic differences based on gender or age.1

Clearance not dependent on hepatic or renal function; therefore, pharmacokinetics not expected to be influenced by hepatic or renal impairment.1

Stability

Storage

Parenteral

Injection

2–8°C.1

Store diluted solution at room temperature or under refrigeration for ≤24 hours.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility1

Compatible

Sodium chloride 0.9%

Actions

  • Potent vasoconstrictor that increases BP in patients with septic or other forms of distributive shock.1 5 9

  • Synthetic preparation of endogenous human angiotensin II, a peptide hormone of the RAAS.1 3 4 5 7 9

  • Increases BP through direct vasoconstriction of the peripheral vasculature; other effects include aldosterone secretion, vasopressin release, activation of the sympathetic nervous system, cardiac remodeling, and preferential vasoconstrictive effects on renal efferent arterioles.1 3 4 5 8 9

  • Vasoconstrictive effects are mediated by G-protein-coupled angiotensin II receptor type 1 on vascular smooth muscle cells.1 5 8 9

Advice to Patients

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Angiotensin II Acetate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Concentrate for injection, for IV infusion

2.5 mg/mL (of angiotensin II)

Giapreza

La Jolla

AHFS DI Essentials™. © Copyright 2021, Selected Revisions November 4, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. La Jolla. Giapreza (angiotensin II) injection for intravenous infusion prescribing information. San Diego, CA; 2017 Dec.

2. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377.

3. Busse LW, Wang XS, Chalikonda DM, et al. Clinical Experience With IV Angiotensin II Administration: A Systematic Review of Safety. Crit Care Med. 2017 Aug;45(8):1285-1294.

4. Khanna A, English SW, Wang XS, et al. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med 2017; 377:419-430.

5. Bussard RL, Busse LW. Angiotensin II : a new therapeutic option for vasodilatory shock. Therapeutics and Clinical Risk Management. 2018:14 1287–1298.

6. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 209360Orig1s000: Summary review. From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209360Orig1s000SumR.pdf

7. . Angiotensin II (Giapreza) for septic shock. Med Lett Drugs Ther. 2018; 60:199-200. http://www.ncbi.nlm.nih.gov/pubmed/30653477?dopt=AbstractPlus

8. Rodriguez R and Fernandez EM. Role of angiotensin II in treatment of refractory distributive shock. Am J Health Syst Pharm. 2019; 76: 101-107.

9. Antonucci E, Gleeson PJ, Annoni F et al. Angiotensin II in Refractory Septic Shock. Shock. 2017; 47:560-566. http://www.ncbi.nlm.nih.gov/pubmed/27879559?dopt=AbstractPlus

10. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 209360Orig1s000: Clinical Pharmacology and Biopharmaceutics Review. From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209360Orig1s000ClinPharmR.pdf